Abstract 4732
Background
The use of progesterone receptor (PR) ligands for adjuvant breast cancer treatment remains controversial. We propose that antiprogestins inhibit the breast tumor growth with high isoform A (PRA)/isoform B (PRB) ratio while progestins may inhibit those with opposite ratios.
Methods
We used metastatic models with different PR isoform ratios to evaluate the effect of antiprogestins [mifepristone (MFP), aglepristone (AGLE), telapristone acetate (TLP), ulipristal acetate (UPA), or progestins [medroxyprogesterone acetate (MPA) or progesterone (Pg)]. Murine BALB/c tumors with PRA>PRB (C7-2-HI) and PRB>PRA (C7-HI), human MDA-MB-231 cells transfected with PRB and the inducible MDA-MB-231-iPRAB cells were inoculated into NSG mice.
Results
All antiprogestins inhibited C7-2-HI tumor growth rate (MFP 88%, TLP 59% UPA 70%) and the onset of lymph node and lung metastasis. AGLE induced complete tumor regression. The progestin MPA, increased tumor size and metastasis in a 60% (p < 0.001) and Pg showed a similar trend (22%). MFP and AGLE also inhibited the tumor growth and number of metastatic foci of the MDA-MB-231-iPRAB expressing PRA. Onset of long-term metastasis was evaluated by tumor surgery after interruption of MFP or AGLE neoadyuvant treatment. Both antiprogestins increased the Disease Free Survival rate (p < 0.001) compared with controls. Six out of 8 and 3/5 mice receiving AGLE and MFP, respectively, are disease free one year after surgery. AGLE adjuvant treatment, also inhibited long-term metastasis (p < 0.001). With C7-HI model (PRB>PRA), AGLE, UPA or MFP increased tumor growth and/or metastasis (p < 0.001) whereas MPA showed an opposite trend in the number of metastatic foci. Experiments performed with the MDA-MB-231 cells transfected with or induced to express PRB confirmed the inhibitory effects of MPA on the metastatic development.
Conclusions
Progestins/antiprogestins stimulate or inhibit, respectively tumor growth/metastasis of mammary carcinomas with high PRA/PRB ratio, and they may exert opposite effects in tumors with low PRA/PRB ratio. These findings highlight the relevance of evaluating PR isofor.m ratio prior to PR ligand treatment on human breast cancer.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
CONICET.
Funding
CONICET; INC, ANPCYT.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3139 - Efficacy and safety of FOLFIRI/Aflibercept (FA) in elderly population with mCRC after failure of oxaliplatin-based chemotherapy.
Presenter: Nieves Martinez Lago
Session: Poster Display session 2
Resources:
Abstract
3446 - Fluoropyrimidine-induced cardiotoxicity in colorectal cancer patients: preliminary data from the prospective observational CHECKPOINT trial (NCT02665312)
Presenter: Pasquale Lombardi
Session: Poster Display session 2
Resources:
Abstract
3969 - Comparable survival outcome between Thai patients with sporadic young adult and adult onset colorectal cancer
Presenter: Kanjana Sukhokanjanachusak
Session: Poster Display session 2
Resources:
Abstract
4455 - Impact of primary tumor side on 3-year survival outcomes of first-line (1L) FOLFOX-4 ± cetuximab in patients with RAS wild-type (wt) metastatic colorectal cancer (mCRC) in the phase 3 TAILOR trial
Presenter: Shukui Qin
Session: Poster Display session 2
Resources:
Abstract
4481 - Undetectable RAS mutant clones in plasma: possible implication for therapy and prognosis in the patient with RAS mutant metastatic colorectal cancer?
Presenter: Mohamed Bouchahda
Session: Poster Display session 2
Resources:
Abstract
5074 - Dihydropyrimidine dehydrogenase (DPD) determination prior the administration of medicines containing fluorouracil: a single Spanish hospital experience.
Presenter: Maria Dolores Mediano Rambla
Session: Poster Display session 2
Resources:
Abstract
5242 - Differences in survival between right and left-sided colorrectal cancer (CRC) in every stage, a CARESS-CCR Group Study.
Presenter: Julia Alcaide-Garcia
Session: Poster Display session 2
Resources:
Abstract
1123 - Quality of Life (QoL) in patients with aflibercept (AFL) and FOLFIRI for metastatic colorectal cancer (mCRC) – Interim analysis with focus on mutational status of the non-interventional study QoLiTrap (AIO-LQ-0113)
Presenter: Roger von Moos
Session: Poster Display session 2
Resources:
Abstract
1212 - The cost of adverse event management in patients with RAS wild-type metastatic colorectal cancer treated with first-line cetuximab and panitumumab: an Italian healthcare payer perspective
Presenter: Karl Patterson
Session: Poster Display session 2
Resources:
Abstract
1619 - Meta-analysis of KRAS Mutation as prognostic factor in patients (pts.) with resection of colorectal (CRC) liver metastases: Tumor burden and Sideness analysis.
Presenter: Maria Romina Luca
Session: Poster Display session 2
Resources:
Abstract